The overall goal of the proposed experiments is to characterize the mechanisms that regulate the activity-dependent translation and degradation of Fragile X mental retardation protein (FMRP). Fragile X syndrome is the most common form of inherited mental retardation. This disease is caused by transcriptional silencing of the FMR1 gene and thus loss of expression of FMRP. Recent work indicates that FMRP is an RNA-binding protein involved in the regulation of protein synthesis-dependent synaptic plasticity. Furthermore, FMRP itself may be subject to translational regulation by synaptic activation. Preliminary studies from our laboratory indicate that: 1) visual experience induces transient expression of FMRP in the visual cortex of dark reared/light exposed rats; 2) cytoplasmic polyadenylation element and the CPE binding protein may play a role in the translational activation of FMR1 mRNA following visual experience; 3) the ubiquitin system may be involved in the rapid disappearance of FMRP. The translation and subsequent rapid degradation of FMRP could be important factors in regulating protein synthesis-dependent synaptic modification. In the proposed experiments we will further elucidate the cellular and molecular mechanisms that regulate FMRP expression during synaptic plasticity.